New Investigator Research Grant Program

Acute myeloid leukemia (AML) is an aggressive blood cancer with over 20,000 new diagnosis each year. Despite decades of intensive research, most AML patients die of their disease within 5 years. AML is caused by mutations in genes, and which genes are mutated heavily influences a patient’s prognosis. RUNX1 is one of the most commonly mutated genes in AML, and RUNX1 mutations are associated with AML that is resistant to chemotherapy, has a high rate of relapse, and early mortality. How RUNX1 mutations lead to poor outcomes is poorly understood, and there are no therapies currently available that target RUNX1 mutations. TurboID is an experimental system used to detect protein interactions using proximity labeling and mass spectrometry. We have used TurboID to identify the protein interactions of unmutated (“wildtype”) RUNX1; these data suggested ways in which mutant RUNX1 may lead to abnormal function. We propose to use the TurboID system to identify protein interactions that differ between wildtype RUNX1, and common RUNX1 mutations found in AML patients. These novel interactions represent attractive targets for therapies that may improve outcomes for AML patients with RUNX1 mutations, and we will use machine learning to define the three-dimensional structure of these novel protein interactions to provide a framework for targeted drug development.